The physiological function and mode of regulation of transglutaminases are being studied as to their role in the formation of "provisional stromata" (fibrin or fibrin-connective tissue), during tissue or bone fracture repair, and in the modulation of specific cellular processes. The coagulant layer formed at injury sites is one of the vital elements of hemostasis and diathesis. The major constituent of this coagulant gel is fibrin. Fibrin stability appears to dictate overall healing and restoration processes and is modulated by factor XIIIa-catalyzed cross- linking of fibrin subunits and of a -antiplasmin to a-chain of fibrin. A number of other plasma proteins are also known to cross-link to fibrin, e.g., fibronectin, thrombospondin and von Wilerbrand Factor. Osteonectin, a non-collagenous bone glycoprotein which exhibits high affinity for type I collagen, thrombospondin and hydroxyapatite was shown to cross-link to fibrin and also found to be a substrate for cellular transglutaminase. Osteonectin was found in plasma and bone as a tight complex wit albumin. Fibrin clots provide matrices for the initial phase of cell migration and anchorage and have been found to be covalently cross-linked to cell membrane (i.e, in B16 melanoma cell). The fibrin cross-linked to fibrin provides a protective shield for melanoma cells against LAK cell-induced cell-lysis. Cellular transglutaminases in terminally differentiated epidermis catalyze the cross-linking of cellular proteins to form stabilized cornified envelope. The main cytosol transglutaminase was shown to occur in an inactive form in the differentiated cells. It was activated by either high calcium concentration or by proteases that are known to be active participants in the terminal differentiation process.